JP2008256721A - Biosensor and biosensor device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a biosensor device measurable without being influenced by viscosity of a sample. <P>SOLUTION: This biosensor device has a biosensor having a plurality of biosensor sections having a working pole and a counter pole, and a signal processing circuit for specifying the concentration of a measuring object substance from its electric current value, by measuring an electric current flowing out of a working pole electrode, by impressing respectively different voltages between the respective working pole and counter pole of the plurality of biosensor sections. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a biosensor and a biosensor device for electrically detecting biological substances such as oligonucleotides, antigens, enzymes, peptides, antibodies, DNA fragments, RNA fragments, glucose, lactic acid and cholesterol, or chemical substances. is there.

  In recent years, the types of biosensing instruments that use disposable sample pieces have been increasing year by year, and in particular, all the proteins that are produced at a certain point in time, in particular components in biological fluids such as blood, plasma, urine and saliva. That is, it is expected to measure and analyze the proteome easily and in a short time. Further, in the near future, it is expected that tailor-made medical treatment for performing treatment or medication in accordance with individual SNP (abbreviation of Single Nucleotido Polymorphism) information is expected by genetic diagnosis using a disposable DNA chip. Among biosensing measuring instruments, biosensors using enzymes that promote chemical reactions such as blood glucose levels and lactic acid levels are already widely used.

  Hereinafter, a biosensor device used for detecting the amount of glucose in a blood sample, that is, a blood glucose level, disclosed in Patent Document 1 as a conventional example will be described. In the present specification, the “biosensor” refers to a disposable part including a detection unit for a chemical substance such as a biological substance, and the “biosensor unit” refers to a set of working electrodes of the biosensor. A portion having a counter electrode is referred to, and the “biosensor chip” refers to a disposable portion in which a biosensor and a measurement circuit are mounted on a substrate. In addition, the “biosensor device” refers to the entire device in which an analysis circuit, a display device, and the like are added to a biosensor or a biosensor chip.

  FIG. 25 is a block circuit diagram showing the structure of a conventional biosensor device. As shown in the figure, a conventional biosensor device includes a biosensor 1501 that generates an electric signal by detecting a component to be measured contained in a sample, and a measurement circuit for processing the electric signal generated by the biosensor 1501. 1509. Although not shown, the conventional biosensor device is provided with an analysis circuit for analyzing the data obtained by the measurement circuit 1509, a display unit for displaying the measurement result and the analysis result, and the like as necessary. .

  The biosensor 1501 has a working electrode (anode) 1510 formed in the reaction chamber and a counter electrode (cathode) 1511 facing the working electrode 1510 with a space for filling the sample. The counter electrode 1511 is coated with a reaction reagent (not shown) made of an enzyme, mediator, microorganism, or the like corresponding to the component to be measured.

  The measurement circuit 1509 includes a working electrode 1503 connected to the working electrode 1510 via the conductive wiring in the biosensor 1501 during measurement, a counter electrode 1504 connected to the counter electrode 1511 via the conductive wiring during measurement, A first voltage source 1505a connected to the working electrode 1503, a second voltage source 1506 connected to the counter electrode 1504, and the first voltage source 1505a have a working electrode control voltage Vpr1. The second voltage source 1506 includes a reference voltage source 1508 for supplying a counter electrode control voltage Vmr1 and a signal processing circuit 1507 connected to the first voltage source 1505a.

  In the conventional biosensor device, the working electrode 1503 and the counter electrode 1504 refer to the working electrode control voltage Vpr1 and the counter electrode control voltage Vmr1 generated by the reference voltage source 1508, respectively. That is, the voltage Vp1 of the working electrode 1503 is applied by the first voltage source 1505a to the same voltage as the working electrode control voltage Vpr1. The voltage Vm1 of the counter electrode 1504 is applied by the second voltage source 1506 to the same voltage as the counter electrode control voltage Vmr1.

Vp1 = Vpr1 (1)
Vm1 = Vmr1 (2)
Therefore, a biosensor applied voltage Vf1 that is a differential voltage between the working electrode control voltage Vpr1 and the counter electrode control voltage Vmr1 is applied between the working electrode 1510 and the counter electrode 1511 of the biosensor 1501.

Vf1 = Vp1-Vm1 = Vpr1-Vmr1 (3)
In this state, when a blood sample is applied to the biosensor 1501, the reaction between the reagent and the substance to be measured in the blood starts. As a result, the working electrode current If1 starts to flow. The first voltage source 1505a having an ammeter measures the working electrode current If1 and outputs a working electrode current amount signal s1517, which is the measurement result, to the signal processing circuit 1507. Next, the signal processing circuit 1507 calculates the blood glucose level by calculating the working electrode current amount signal s1517. For example, when the biosensor device has a display device, the measurement value is displayed on the display device.

  FIG. 26 is a diagram showing the measurement operation of the conventional biosensor device shown in FIG. 25 over time.

  The voltage graph on the upper side of the figure shows that in the blood glucose level measurement, a biosensor applied voltage Vf1 that is a differential voltage between the working electrode control voltage Vpr1 and the counter electrode control voltage Vmr1 is applied to the biosensor 1501. The charge graph on the lower side of FIG. 26 shows the time change of the integrated value of the working electrode current If1 related to the blood glucose level. The relationship between the charge amount Q and the working electrode current If1 is expressed by the following equation (4).

Charge amount Q = ∫ (If1) dt (4)
At the time t = 0 (s), the reaction with the reagent starts at the same time as the blood sample is applied. Then, the charge starts to be generated with the start of the reaction, and when the blood sugar finally disappears, the reaction is stopped and the generation of the charge is also eliminated. The blood glucose level can be obtained by measuring the charge amount Q after the point at which the generation of electric charge ceases.

  27 is a block circuit diagram showing an example of the circuit configuration of the first voltage source 1505a and the second voltage source 1506 having an ammeter in the biosensor device shown in FIG. FIG. 28 is a plan view showing a configuration example of the biosensor 1501. FIG. 29 is a plan view showing a configuration example of the biosensor chip 1520 when the biosensor 1501 and the measurement circuit 1509 are made into one chip and made disposable.

As shown in FIG. 27, the first voltage source 1505a has a circuit configuration in which a feedback resistor 1518 is negatively fed back to an operational amplifier, and the second voltage source 1506 has an operational amplifier in a null-amplifier configuration, that is, a buffer circuit configuration. Thus, the above-described function is realized.
JP 2002-340853 A (FIG. 7)

  FIG. 30 is a diagram schematically showing a relationship between a blood glucose level, a blood sample viscosity, and a biosensor applied voltage Vf1 in the conventional biosensor device, and FIG. It is a figure which shows biosensor applied voltage Vf1 and the actual charge amount Q. Here, in FIG. 30, “BSL” means a blood sugar level.

  In the measurement using the biosensor device, by applying a voltage between the working electrode 1510 and the counter electrode 1511 of the biosensor 1501, the reaction between the blood glucose and the reagent (or the blood glucose reaction catalyzed by the reagent) is promoted. An electric field is generated inside. Polarized fine particle components such as blood cells move in the chamber by the electric field, and the reaction is promoted. However, when the viscosity of the blood is high, the movement of the fine particle component is hindered, so that the reaction is inhibited. Therefore, as shown in FIG. 30 and FIG. 31, since the reaction with the reagent is inhibited as the viscosity of the blood sample increases, the blood sugar level display appears lower.

  Furthermore, as the biosensor applied voltage Vf1 decreases, the electric field in the reaction chamber also decreases proportionally, and the amount of the polarized fine particle component in the blood that moves in the chamber also decreases proportionally. As a result, when the biosensor applied voltage Vf1 is low, it is particularly susceptible to the viscosity of the blood sample. As described above, the conventional biosensor device has a problem in that the reaction amount of the sample with the viscosity reagent is reduced, and the blood glucose level display is low.

  An object of the present invention is to provide a biosensor, a biosensor chip, and a biosensor device that can perform accurate measurement regardless of the viscosity of a sample.

  In order to solve this problem, a first biosensor device of the present invention includes a working electrode and a counter electrode facing the working electrode with an interval for flowing a fluid to be inspected containing a substance to be measured. A biosensor having a biosensor part, a measurement circuit for applying a voltage between the working electrode and the counter electrode during measurement, and measuring the concentration of the substance to be measured from the current flowing through the biosensor part; The measurement circuit is configured to change the voltage applied between the working electrode and the counter electrode over time.

  With this configuration, when the fluid to be inspected is blood containing charged fine particles, the microparticles are moved by the applied voltage from the measurement circuit and the fluid to be inspected is agitated. Both accuracy can be realized. Therefore, according to the biosensor device of the present invention, accurate measurement can be performed regardless of the viscosity of the fluid to be inspected.

  For example, the measurement circuit includes a working electrode connected to the working electrode, a first voltage source that applies a first voltage to the working electrode, a counter electrode connected to the counter electrode, and the counter electrode A second voltage source for applying a second voltage to the electrode; an ammeter added to at least one of the first voltage source or the second voltage source; and the first voltage source including the first voltage source. A reference voltage source that supplies a working electrode control voltage equal to a voltage of 1 and a counter electrode control voltage equal to the second voltage to the second voltage source, the first voltage source, and the second voltage source, respectively. The signal processing circuit for processing the electric current amount signal output according to the electric current which flows through the said biosensor from the voltage source to which the said ammeter was added among voltage sources may be sufficient.

  The measurement circuit can reduce the measurement time and improve the measurement accuracy by applying a voltage biased with a constant voltage and modulated with a rectangular wave to at least one of the working electrode and the counter electrode. it can.

  The measurement circuit applies a voltage biased with a constant voltage and modulated with a diffusion code to at least one of the working electrode and the counter electrode, whereby a plurality of types of fine particles having different resonance frequencies are generated in the fluid to be inspected. Even if it is contained, the fluid to be inspected can be effectively stirred, so that the measurement time can be shortened and the measurement accuracy can be improved as compared with the conventional biosensor device.

  The measurement circuit may be configured to apply a voltage biased with a constant voltage and modulated with a sine wave to at least one of the working electrode and the counter electrode.

  In this case, the measurement circuit further includes a voltage source with a low-pass filter connected to the working electrode or the counter electrode, and a ΔΣ modulator connected to the voltage source with the low-pass filter, and modulates with the sin wave. Since the generated voltage is generated by the serial connection of the ΔΣ modulator and the voltage source with the low-pass filter, a sin wave can be generated using a digital circuit, so an analog circuit or the like is used. Compared to the case, the circuit area can be reduced.

  The second biosensor device of the present invention has a plurality of biosensor units including a working electrode and a counter electrode facing the working electrode with an interval for allowing a fluid to be inspected containing a substance to be measured to flow in. Applying different voltages between the biosensor and the working electrode and the counter electrode of the biosensor unit at the time of measurement, and based on the current flowing from the working electrode or the counter electrode of the biosensor unit And a measurement circuit for measuring the concentration of the substance to be measured.

  With this configuration, it is possible to estimate the viscosity of the fluid to be inspected by measuring signals from the biosensor unit to which different voltages are applied. Since the actual measurement value can be corrected based on the viscosity of the fluid to be inspected, a more accurate measurement value than before can be obtained by using the biosensor device of the present invention.

  The measurement circuit measures only the current flowing from the working electrode or the counter electrode by measuring the concentration of the substance to be measured based on the current flowing from the working electrode and the current flowing from the counter electrode of each biosensor unit. Compared with the measurement accuracy can be increased.

  The biosensor further includes a sample spotting portion for spotting the fluid to be tested, and a capillary tube for supplying the fluid to be tested to each biosensor portion, and a plurality of the biosensor portions Are connected to each other in series when viewed from the sample spot by the capillary, for example, when the current from the biosensor near the sample spot is detected and far from the sample spot The viscosity of the fluid to be inspected can be obtained by detecting the difference from the time when the current from the other biosensor unit is detected. And it becomes possible by performing correction | amendment according to the obtained viscosity to be more exact and more accurate than before.

  In addition, the biosensor further includes a sample spotting unit for spotting the fluid to be tested, and a capillary tube for supplying the fluid to be tested to each biosensor unit. When the sensor units are connected in parallel to each other as viewed from the sample spotting unit by the capillaries, and the capillaries for supplying the fluid to be tested to the biosensor units have different sizes, the respective capillaries The viscosity of the fluid to be inspected can be determined from the difference in time passing through Therefore, by correcting the actual measurement value based on the obtained viscosity value, it becomes possible to perform measurement with higher accuracy and higher accuracy than before.

  Alternatively, the biosensor includes a sample spotting portion for spotting the fluid to be tested, and first capillaries and first capillaries having different sizes for supplying the fluid to be tested to the biosensor portions. And a plurality of biosensor parts, and at least two of the plurality of biosensor parts are separated from the sample spotting part by the first capillary. Are connected in series with each other, and at least two of the plurality of biosensor parts are connected in series with each other when viewed from the sample spotting part by the second capillary tube, The biosensor part connected to the capillary and the biosensor part connected to the second capillary are connected in parallel to each other when viewed from the sample spotting part. And, since the arrival time difference of the measurement circuit of the current flowing from the biosensor unit can more measurements, it is possible to perform measurement of higher accuracy.

  Since the characteristics of the plurality of biosensor parts are different from each other, the viscosity of the fluid to be inspected is obtained from the difference in the arrival time of the current flowing through each biosensor part to the measurement circuit and the difference in the actual measurement value. It becomes possible to correct.

  The third biosensor of the present invention includes a plurality of biosensor parts including a working electrode and a counter electrode facing the working electrode with an interval for allowing a fluid to be inspected containing a substance to be measured to flow in, A biosensor having a sample spotting section for spotting the fluid to be tested, a capillary for supplying the fluid to be tested to each biosensor section, and the actions of each of the biosensor sections during measurement A measuring circuit for applying a voltage between the electrode and the counter electrode and measuring the concentration of the substance to be measured based on a current flowing from the working electrode or the counter electrode of each biosensor unit. In the biosensor device, the plurality of biosensor units are connected to each other in series by the capillary tube as viewed from the sample spotting unit.

  As a result, as described above, it is possible to realize measurement that is more accurate and accurate than the conventional one.

  A fourth biosensor device according to the present invention includes a plurality of biosensor units including a working electrode and a counter electrode facing the working electrode with an interval for allowing a fluid to be inspected containing a substance to be measured to flow in. A biosensor having a sample spotting portion for spotting the fluid to be tested, a capillary for supplying the fluid to be tested to each biosensor portion, and the action of each of the biosensor portions during measurement A measuring circuit for applying a voltage between the electrode and the counter electrode and measuring the concentration of the substance to be measured based on a current flowing from the working electrode or the counter electrode of each biosensor unit. In the biosensor device, the plurality of biosensor units are connected in parallel to each other when viewed from the sample spotting unit by the capillary, and supply the fluid to be tested to each biosensor unit By the size of the order of the capillary are different from each other, it is possible to measure the concentration accurately measured substance than before.

  A fifth biosensor device according to the present invention includes a plurality of biosensor units each including a working electrode and a counter electrode facing the working electrode with an interval for flowing a fluid to be inspected containing a substance to be measured. A biosensor having a sample spotting portion for spotting the fluid to be tested, a first capillary and a second capillary for supplying the fluid to be tested to each biosensor portion, and during measurement A voltage is applied between each working electrode and the counter electrode of the biosensor unit, and the concentration of the substance to be measured is measured based on a current flowing from the working electrode or the counter electrode of each biosensor unit. The first capillary and the second capillary are different in size from each other, and at least two of the plurality of biosensor units are provided. of The Io sensor parts are connected to each other in series when viewed from the sample spotting part by the first capillary, and at least two of the plurality of biosensor parts are sampled by the second capillary. The biosensor part connected to the first capillary tube and the biosensor part connected to the second capillary tube are connected in series as viewed from the landing part, and the biosensor part connected to the second capillary tube is parallel to each other as viewed from the sample spotting part. It is connected to the.

  With this configuration, the difference in arrival time of the current flowing from each biosensor unit to the measurement circuit can be measured more, so that it is possible to perform measurement with higher accuracy.

  A sixth biosensor device according to the present invention includes a working electrode and a counter electrode facing the working electrode with an interval for allowing a fluid to be inspected containing a substance to be measured to flow therein, and having different characteristics from each other A voltage applied between the working electrode and the counter electrode of each of the biosensor units at the time of measurement, and a current flowing from the working electrode or the counter electrode of each biosensor unit. And a measurement circuit for measuring the concentration of the substance to be measured based on the measurement circuit.

  With this configuration, it is possible to correct the measured value according to the viscosity of the fluid to be inspected based on the difference in the arrival time of the current flowing from each of the biosensor units or the difference in the measured value. Accurate and highly accurate measurement can be performed.

  A first biosensor chip according to the present invention includes a biosensor unit including a working electrode and a counter electrode facing the working electrode with a space for flowing a fluid to be inspected containing a substance to be measured. And a voltage applied between the working electrode and the counter electrode at the time of measurement, and the concentration of the substance to be measured is measured from the current flowing through the biosensor unit. The measurement circuit changes the voltage applied between the working electrode and the counter electrode over time.

  With this configuration, it becomes possible to measure a substance to be measured with higher accuracy and in a shorter time than in the past. In addition, since the entire measurement circuit can be disposable, for example, when measuring a plurality of types of substances, the main body of the biosensor device can be shared.

  The second biosensor chip of the present invention has a plurality of biosensor parts including a working electrode and a counter electrode facing the working electrode with an interval for allowing a fluid to be inspected containing a substance to be measured to flow in. A biosensor is provided on the same substrate as the biosensor, applies different voltages between the working electrode and the counter electrode of the biosensor unit during measurement, and the biosensor unit A measuring circuit for measuring the concentration of the substance to be measured based on a current flowing from the working electrode or the counter electrode.

  With this configuration, it is possible to realize measurement with higher accuracy than before and to perform concentration measurement of a plurality of types of substances to be measured by sharing the biosensor device body.

  A third biosensor chip according to the present invention includes a plurality of biosensor units each including a working electrode and a counter electrode facing the working electrode with an interval for flowing a fluid to be inspected containing a substance to be measured. A biosensor having a sample spotting section for spotting the fluid to be tested, and a capillary tube for supplying the fluid to be tested to each biosensor section, and provided on the same substrate as the biosensor A voltage is applied between each working electrode and the counter electrode of the biosensor unit at the time of measurement, and based on a current flowing from the working electrode or the counter electrode of each biosensor unit, A biosensor chip including a measurement circuit for measuring concentration, wherein the plurality of biosensor units are connected in series with each other as viewed from the sample spotting unit by the capillary. There.

  With this configuration, it is possible to realize measurement with higher accuracy than before and to perform concentration measurement of a plurality of types of substances to be measured by sharing the biosensor device body.

  A fourth biosensor chip according to the present invention includes a plurality of biosensor portions each including a working electrode and a counter electrode facing the working electrode with an interval for allowing a fluid to be inspected containing a substance to be measured to flow. A biosensor having a sample spotting section for spotting the fluid to be tested, and a capillary tube for supplying the fluid to be tested to each biosensor section, and provided on the same substrate as the biosensor A voltage is applied between each working electrode and the counter electrode of the biosensor unit at the time of measurement, and based on a current flowing from the working electrode or the counter electrode of each biosensor unit, A biosensor chip including a measurement circuit for measuring concentration, wherein the plurality of biosensor units are connected in parallel to each other as viewed from the sample spotting unit by the capillaries. The size of the capillaries for supplying the inspection fluid to each biosensor section are different from each other.

  With this configuration, it is possible to realize measurement with higher accuracy than before and to perform concentration measurement of a plurality of types of substances to be measured by sharing the biosensor device body.

A fifth biosensor chip according to the present invention includes a plurality of biosensor units each including a working electrode and a counter electrode facing the working electrode with an interval for allowing a fluid to be inspected containing a substance to be measured to flow in. A biosensor having a sample spotting portion for spotting the fluid to be tested, a first capillary and a second capillary for supplying the fluid to be tested to each biosensor portion, and the bio A current that is provided on the same substrate as the sensor, applies a voltage between each working electrode and the counter electrode of the biosensor unit during measurement, and flows from the working electrode or the counter electrode of each biosensor unit And a measurement circuit for measuring the concentration of the substance to be measured, wherein the first capillary and the second capillary are different in size from each other. Of the biosensor parts, at least two biosensor parts are connected in series with each other as seen from the sample spotting part by the first capillary tube, and at least two of the plurality of biosensor parts. The biosensor portion is connected in series with each other as viewed from the sample spotting portion by the second capillary, and the biosensor portion connected to the first capillary and the biosensor connected to the second capillary The parts are connected in parallel with each other when viewed from the sample spotting part.

  With this configuration, it is possible to realize measurement with higher accuracy than before and to perform concentration measurement of a plurality of types of substances to be measured by sharing the biosensor device body. In particular, the biosensor chip of the present invention is preferably used when high accuracy is required as compared with the third and fourth biosensor chips.

  A sixth biosensor chip of the present invention includes a working electrode and a counter electrode facing the working electrode with an interval for allowing a fluid to be inspected containing a substance to be measured to flow therein, and having different characteristics from each other A biosensor having a plurality of parts, and a voltage applied between the working electrode and the counter electrode of the biosensor part, provided on the same substrate as the biosensor, and each biosensor And a measuring circuit for measuring the concentration of the substance to be measured based on the current flowing from the working electrode or the counter electrode of the unit.

  With this configuration, it is possible to realize measurement with higher accuracy than before and to perform concentration measurement of a plurality of types of substances to be measured by sharing the biosensor device body.

  A first biosensor of the present invention includes a plurality of biosensor units including a working electrode and a counter electrode facing the working electrode with an interval for flowing a fluid to be inspected containing a substance to be measured, A biosensor having a sample spotting portion for spotting a fluid to be tested and a capillary tube for supplying the fluid to be tested to each of the plurality of biosensor portions, Each is connected in series by the capillary tube as viewed from the sample spot.

  With this configuration, by combining measurement circuits that can detect currents flowing from the working electrodes or counter electrodes of a plurality of biosensor units, it is possible to perform measurement with higher accuracy than before, regardless of the viscosity of the fluid to be inspected.

  A second biosensor of the present invention includes a plurality of biosensor units including a working electrode and a counter electrode facing the working electrode with an interval for flowing a fluid to be inspected containing a substance to be measured, A biosensor having a sample spotting portion for spotting a fluid to be tested and a capillary tube for supplying the fluid to be tested to each of the plurality of biosensor portions, The capillaries are connected in parallel to each other as viewed from the sample spotting portion by the capillaries, and the capillaries for supplying the fluid to be tested to the biosensor portions have different sizes.

  With this configuration, by combining measurement circuits that can detect currents flowing from the working electrodes or counter electrodes of a plurality of biosensor units, it is possible to perform measurement with higher accuracy than before, regardless of the viscosity of the fluid to be inspected.

  A third biosensor of the present invention includes a plurality of biosensor units including a working electrode and a counter electrode facing the working electrode with an interval for flowing a fluid to be inspected containing a substance to be measured, A biosensor having a sample spotting portion for spotting a fluid to be tested, and a first capillary and a second capillary for supplying the fluid to be tested to each of the plurality of biosensor portions. The first capillary tube and the second capillary tube are different in size from each other, and at least two of the plurality of biosensor units are connected to the sample spotting unit by the first capillary tube. And at least two biosensor parts among the plurality of biosensor parts are connected in series with each other as seen from the sample spotting part by the second capillary tube. The above biosensor portion connected to the capillary and the said biosensor unit connected to the second capillary are connected in parallel to each other when viewed from the sample adhering part.

  With this configuration, by combining measurement circuits that can detect currents flowing from the working electrodes or counter electrodes of a plurality of biosensor units, it is possible to perform measurement with higher accuracy than before, regardless of the viscosity of the fluid to be inspected.

  A fourth biosensor of the present invention includes a working electrode and a counter electrode having a characteristic different from each other, including a working electrode and a counter electrode facing the working electrode with an interval for flowing a fluid to be inspected containing a substance to be measured. It has a plurality.

  With this configuration, by combining measurement circuits that can detect currents flowing from the working electrodes or counter electrodes of a plurality of biosensor units, it is possible to perform measurement with higher accuracy than before, regardless of the viscosity of the fluid to be inspected.

  As described above, according to the biosensor device of the present invention, a biosensor unit including a working electrode and a counter electrode facing the working electrode with a space for flowing a fluid to be inspected containing a substance to be measured. And a measurement circuit for applying a voltage between the working electrode and the counter electrode at the time of measurement and measuring the concentration of the substance to be measured from a current flowing through the biosensor unit. In the sensor device, the measurement circuit can realize a reduction in measurement time and high accuracy by changing a voltage applied between the working electrode and the counter electrode with time. For this purpose, for example, a voltage having a rectangular wave at the counter electrode or working electrode, a voltage obtained by modulating the bias voltage with a spreading code, a voltage obtained by modulating the bias voltage with a sin wave, or the like may be applied.

  Embodiments according to the present invention will be described below with reference to FIGS.

(First embodiment)
FIG. 1 is a block circuit diagram showing the biosensor device according to the first embodiment of the present invention, and FIG. 2 shows the relationship between the biosensor applied voltage Vf1 and the charge amount Q in the biosensor device of the present embodiment. FIG.

  The configuration of the biosensor device of this embodiment shown in FIG. 1 is almost the same as that of the conventional biosensor device shown in FIG. 25, but only the waveform of the counter electrode control voltage Vmr1 output from the reference voltage source 508 is different.

  That is, the biosensor device of the present embodiment detects the component to be measured included in the sample that is a fluid and generates an electrical signal, and the electricity generated in the first biosensor unit 501. And a measurement circuit 509 for processing the signal. Although not shown, the biosensor device of the present embodiment is provided with an analysis circuit for analyzing data obtained by the measurement circuit 509, a display unit for displaying the measurement result and the analysis result, and the like as necessary. ing. When the first biosensor unit 501 is removable and disposable from the apparatus main body, or the semiconductor chip on which the first biosensor unit 501 and the measurement circuit are mounted is removable from the apparatus main body and becomes disposable. There are cases.

  The first biosensor unit 501 includes a working electrode (anode) 510 formed in the reaction chamber, a working electrode terminal connected to the working electrode 510, and a working electrode 510 with an interval for the sample to flow in. It has a counter electrode (cathode) 511 and a counter electrode terminal connected to the counter electrode 511. The working electrode 510 and the counter electrode 511 have a reaction reagent (non-reactant) composed of an enzyme, mediator, microorganism, or the like corresponding to the component to be measured. (Shown) is applied.

  On the other hand, the measurement circuit 509 is connected to the working electrode 503 connected to the working electrode 510 via the conductive wiring in the first biosensor unit 501 at the time of measurement, and to the counter electrode 511 via the conductive wiring at the time of measurement. A counter electrode 504 having a current meter, a first voltage source 505a connected to the working electrode 503, a second voltage source 506 connected to the counter electrode 504, and a first voltage source 505a. Has a reference voltage source 508 for supplying a working electrode control voltage Vpr1 and a second voltage source 506 for supplying a counter electrode control voltage Vmr1, and a signal processing circuit 507 connected to the first voltage source 505a. Yes.

  In the biosensor device of the present embodiment, the working electrode 503 and the counter electrode 504 receive the working electrode control voltage Vpr1 and the counter electrode control voltage Vmr1 generated by the reference voltage source 508, as in the conventional biosensor device. Refers to each. That is, as the voltage Vp1 of the working electrode 503, the same voltage as the working electrode control voltage Vpr1 is applied by the first voltage source 505a. The voltage Vm1 of the counter electrode 504 is applied by the second voltage source 506 to the same voltage as the counter electrode control voltage Vmr1.

  The biosensor device of this embodiment is different from the conventional biosensor device in that one or both of the counter electrode control voltage Vmr1 and the working electrode control voltage Vpr1 output from the reference voltage source 508 are as shown in FIG. It is not constant but changes over time.

  In the example shown in FIG. 2, the counter electrode control voltage Vmr1 is a voltage that is biased with a constant voltage and modulated with a rectangular wave. Here, “Vmr1 is biased at a constant voltage” means that the center value of Vmr1 is given at a constant voltage (DC). Therefore, a rectangular wave voltage Vm1 equal to the counter electrode control voltage Vmr1 is applied to the counter electrode 504 at the time of measurement. On the other hand, the working electrode control voltage Vpr1 is a constant voltage. Therefore, the voltage Vp1 of the working electrode 503 is also a constant voltage equal to the working electrode control voltage Vpr1. At this time, the range of the biosensor applied voltage Vf1, which is the difference between the working electrode control voltage Vpr1 and the counter electrode control voltage Vmr1, is not particularly limited.

  Thereby, the electric field in the reaction chamber of the first biosensor unit 501 is modulated, and the blood component is electrically stirred in the reaction chamber. As a result, even if the viscosity of the blood sample is high, the reaction with the reagent is promoted, and a decrease in blood glucose level display can be suppressed.

  Note that a circuit for creating a rectangular wave can be easily created using a known technique, but a digital circuit is preferable in order to reduce the circuit area. Alternatively, a circuit that stores a waveform program in a memory or the like in advance and outputs the program may be used.

  As described above, according to the biosensor device of the present embodiment, a biosensor having a working electrode and a counter electrode, a voltage that is modulated with a rectangular wave on one of the working electrode and the counter electrode of the biosensor, and the other. Can be prevented from decreasing the working electrode current If1. Then, the working electrode current amount signal s517 output from the first voltage source 505a is processed by the signal processing circuit, whereby the concentration of the measurement target substance can be specified with higher accuracy and sensitivity than in the past. Moreover, according to the biosensor device of the present embodiment, since the blood sample is effectively stirred, the reaction by an enzyme or the like is promoted, and the measurement time can be shortened. Although the brewing period cannot be generally described, it can be, for example, less than 10 seconds.

  In the present embodiment, the blood glucose level sensor has been described as an example, but the substance to be measured may be any substance that selectively reacts with a reagent such as an enzyme in a sample solution to generate electrons. For example, by selecting an appropriate reagent, measurement of glucose oligonucleotides, antigens, enzymes, peptides, antibodies, DNA fragments, RNA fragments, lactic acid, cholesterol, and the like can be performed with the biosensor device of this embodiment. The same applies to the following embodiments.

  Further, the example in which the counter electrode control voltage Vmr1 is a rectangular wave has been described above, but the same effect as described above can be obtained even if the working electrode control voltage Vpr1 is changed to a rectangular wave, and the counter electrode control voltage Vmr1 and the working electrode control are controlled. Both of the voltages Vpr1 may be rectangular waves whose phases are shifted.

(Second Embodiment)
FIG. 3 is a diagram showing the relationship between the biosensor applied voltage Vf1 and the charge amount Q in the biosensor device according to the second embodiment of the present invention.

  The biosensor device of this embodiment is a modification of the first embodiment, and the circuit configuration thereof is the same as that of the biosensor device of the first embodiment shown in FIG. However, in the biosensor device of this embodiment, as shown in the upper diagram of FIG. 3, the counter electrode control voltage Vmr1 of the counter electrode 504 is biased with a constant voltage and a voltage modulated with a spreading code is applied. . In contrast, the working electrode control voltage Vpr1 is a constant voltage throughout the measurement period.

  As a result, the electric field in the reaction chamber of the first biosensor unit 501 is modulated into a wider frequency spectrum than the rectangular wave used in the first embodiment, so that blood components are electrically generated in the reaction chamber. Agitated randomly. As a result, the blood sample can be stirred regardless of the size of the fine particles contained in the blood, so that the reaction of glucose by the reagent is promoted, and even when the viscosity of the blood sample is high, the decrease in blood sugar level display is suppressed. Can do. Thereby, highly accurate and highly sensitive measurement can be performed. In addition, since the measurement value is less likely to be affected by changes in blood viscosity due to physical condition, errors in the measurement value can be reduced. Furthermore, according to the biosensor device of this embodiment, the blood sample can be effectively stirred by applying a constant voltage and a voltage modulated with a diffusion code to the working electrode and the counter electrode of the biosensor, respectively. It is also possible to shorten the time.

  Note that a circuit for modulating a constant voltage using a spreading code can be easily configured by a known digital or analog circuit.

  In the biosensor device of this embodiment, the working electrode control voltage Vpr1 may be a voltage modulated by a spreading code, or the counter electrode control voltage Vmr1 and the working electrode control voltage Vpr1 may be both modulated by a spreading code. The effect explained in the above can be obtained.

(Third embodiment)
FIG. 4 is a diagram showing the relationship between the biosensor applied voltage Vf1 and the charge amount Q in the biosensor device according to the third embodiment of the present invention. The bioscience device of this embodiment has the circuit configuration shown in FIG. 1 similar to that of the biosensor device of the first and second embodiments, so that the description of the configuration is omitted and the reference numerals of the members are omitted. Reference is made to FIG.

  As shown in FIG. 4, the biosensor device according to the present embodiment is characterized in that the counter electrode control voltage Vmr1 (= Vm1) of the counter electrode 504 is biased with a constant voltage and a voltage modulated with a sin wave is applied. It is that you are. The working electrode control voltage Vpr1 (= Vp1) applied to the working electrode 503 is a constant voltage. Therefore, the magnitude of the biosensor applied voltage Vf1 changes with the period of the sin wave of Vmr1. This sine wave is generated by providing a known sine wave generating circuit inside the reference voltage source 508.

  As a result, the electric field in the reaction chamber of the first biosensor unit 501 is modulated to a single sin wave frequency, so that the blood component having the same natural frequency as the sin wave frequency is contained in the reaction chamber. Is selectively stirred. For this reason, by making the frequency of the counter electrode control voltage Vmr1 coincide with the natural frequency of fine particles such as blood cells and platelets or the natural frequency of the substance to be measured, the blood sample is stirred and the reaction of the substance to be measured by the reagent is promoted. Here, the natural frequency of the fine particles is an audible frequency of several tens of kHz or less, and the natural frequency of a substance to be measured such as glucose is an ultrasonic frequency (MHz level). For this reason, it is particularly preferable to match the frequency of the sin wave with the fine particles in the blood.

  As a result, even when the viscosity of the blood sample is high, it is possible to suppress a decrease in blood glucose level display and perform more accurate measurement. In addition, since the measurement of the substance to be measured can be performed more quickly than before, the measurement time can be shortened.

  In the biosensor device of this embodiment, when the working electrode current If1 flows between the working electrode 510 and the counter electrode 511, the working electrode current signal s517 is output from the first voltage source 505a having an ammeter according to this. Is processed by the signal processing circuit 507, and the blood sugar level is obtained.

  As described above, according to the biosensor device of the present embodiment, the first biosensor unit 501 having the working electrode 510 and the counter electrode 511, and the working electrode 510 and the counter electrode 511 of the first biosensor unit 501. By applying a voltage that is biased with a constant voltage and modulated with a sine wave, measurement time can be shortened and accuracy can be improved.

  In the biosensor device of the present embodiment, the working electrode control voltage Vpr1 may be a voltage modulated by a sine wave, or both the counter electrode control voltage Vmr1 and the working electrode control voltage Vpr1 are modulated by a sine wave, and the phase of each other The effect described above can be obtained even when the voltage is shifted.

(Fourth embodiment)
FIG. 5 is a block circuit diagram showing a biosensor device according to the fourth embodiment of the present invention.

  As shown in the figure, the biosensor device according to the present embodiment is the same as the biosensor device according to the third embodiment except that the first voltage source 505a, the second voltage source 506, and the reference voltage source 508 having an ammeter. Is constituted by a specific circuit.

  In the biosensor device of this embodiment, the voltage modulated by the sin wave is generated by a series connection of a ΔΣ (delta sigma) modulator 8 provided in the reference voltage source 508 and the voltage source 6 with a low-pass filter.

  The first voltage source 505a includes an operational amplifier 550 in which the working electrode control voltage Vpr1 is input to the (+) side input unit and the working electrode 503 is connected to the (−) side input unit, and the operational amplifier 550 The feedback resistor 518 is provided between the output unit and the (−) side input unit.

  In the voltage source 6 with a low-pass filter corresponding to the second voltage source 506 in FIG. 1, the counter electrode control voltage Vmr1 is input to the (+) side input unit during measurement, and the second voltage source 6 is input to the (−) side input unit. The operational amplifier 551 to which the counter electrode control voltage Vmr3 is input and the counter electrode 504 is connected to the output section, the feedback resistor 5 provided between the (−) side input section and the output section of the operational amplifier 551, and the ( -) It is provided between the side input unit and the output unit, and is composed of a feedback resistor 5 and a capacitor 9 connected in parallel.

  In the biosensor device of the present embodiment, the voltage source 6 with a low-pass filter, to which the second counter electrode control voltage Vmr3 having a sin wave signal and the counter electrode control voltage Vmr1 as a bias voltage are input, is applied to the counter electrode 504. Generate a sin wave for.

  Thereby, since the sin wave in the biosensor device of the third embodiment can be generated using a digital circuit, the frequency stability is high and the frequency can be easily switched. Furthermore, a sine wave can be generated with a circuit having a smaller area than an analog circuit.

  As described above, according to the biosensor device of the present embodiment, a biosensor (part) having a working electrode and a counter electrode, and a bias between a working electrode and a counter electrode of the biosensor with a constant voltage, and ΔΣ By applying a voltage modulated by a sin wave generated by the cascade connection configuration of the modulator and the low-pass filter circuit, the measurement time can be shortened, the inspection accuracy can be improved, and the apparatus can be downsized.

(Fifth embodiment)
FIG. 6 is a circuit diagram showing a biosensor device according to the fifth embodiment of the present invention.

  In the biosensor device of the present embodiment shown in the figure, the biosensor 1 is provided with two biosensor units (a first biosensor unit 501 and a second biosensor unit 521) having the same performance. That is, the biosensor 1 includes a first biosensor unit 501 having the same configuration as that of the first to fourth embodiments, and a second electrode having a working electrode 522 and a counter electrode 523 provided to face the working electrode 522. And a biosensor portion 521. In addition, description is abbreviate | omitted about the part which overlaps with the biosensor apparatus of 1st-4th embodiment.

  Further, in the measurement circuit 509, in addition to the first voltage source 505a and the second voltage source 506, a third voltage source 527a connected to the working electrode 522 via the working electrode 3 and a counter electrode 4 and a fourth voltage source 528 connected to the counter electrode 523 via 4.

  The working voltage control voltage Vpr1 is applied to the third voltage source 527a in the same manner as the first voltage source 505a, and a voltage equal to the working electrode control voltage Vpr1 is applied to the working electrode 503 as Vp2.

Vp2 = Vpr1 (5)
The third voltage source 527a has an ammeter similar to the first voltage source 505a, and corresponds to the magnitude of the second working electrode current If2 flowing between the working electrode 522 and the counter electrode 523 during measurement. The magnitude of the working electrode current amount signal s17 is output to the signal processing circuit 507. The fourth voltage source 528 is supplied with the third counter electrode control voltage Vmr2 from the reference voltage source 508, and applies a voltage equal to the third counter electrode control voltage Vmr2 to the counter electrode 4 as Vm2.

Vm2 = Vmr2 (6)
Accordingly, the added second biosensor unit 521 is applied with the biosensor applied voltage Vf2 that is a differential voltage between the working electrode control voltage Vpr1 and the third counter electrode control voltage Vmr2.

Vf2 = Vp2-Vm2 = Vpr1-Vmr2 (7)
When a blood sample is applied to the second biosensor unit 521 added in this state, the reaction with the reagent starts. As a result, the working electrode current If2 starts to be generated. The third voltage source 527a measures the blood glucose level by measuring the working electrode current If2 and calculating the working electrode current amount signal s17, which is the measurement result, in the signal processing circuit 507.

  FIG. 7 is a diagram showing an example of the measurement operation of the biosensor device of the present embodiment shown in FIG. 6 over time. Here, the (first) counter electrode control voltage Vmr1 is higher than the third counter electrode control voltage Vmr2.

Vmr1> Vmr2 (8)
That is,
Vf1 <Vf2 (9)
It is.

  In the voltage graph shown in the upper part of FIG. 7, in the blood glucose level measurement, a biosensor applied voltage Vf2 that is a differential voltage between the working electrode control voltage Vpr1 and the third counter electrode control voltage Vmr2 is applied to the added second biosensor unit 521. Indicates that In addition, the charge graph shown in the lower part of FIG. 7 shows the time change of the integrated value of the working electrode current If2 related to the blood glucose level.

Charge amount Q = ∫ (If2) dt (10)
At the time t = 0 (s), the reaction with the reagent starts at the same time as the blood sample is applied. Along with this, electric charges start to be generated, and when blood sugar is finally lost, the reaction is stopped, and accordingly, no electric charges are generated. The blood glucose level can be obtained by measuring the charge amount Q after that time.

  FIG. 8 shows a circuit configuration example of the first voltage source 505a, the second voltage source 506, the third voltage source 527a, and the fourth voltage source 528 in the biosensor device of this embodiment shown in FIG. It is a block circuit diagram. In the example shown in the figure, the third voltage source 527a has the same configuration as the first voltage source 505a in which the feedback resistor 529 is negatively fed back to the operational amplifier 552. The fourth voltage source 528 has the same configuration as the second voltage source 506 in which the operational amplifier 553 has a Null-amplifier configuration.

  FIG. 9 is a plan view showing a configuration example of the biosensor 1 of the present embodiment. The biosensor 1 is normally removable from the main body. Further, FIG. 10 is a diagram illustrating a configuration example of the biosensor chip 20 in which the biosensor 1 and the measurement circuit 509 are integrated into one chip. FIG. 11 is a diagram in which the principle of the present invention is entered in the performance diagram of the conventional single biosensor shown in FIG. Hereinafter, the operation of the biosensor device of this embodiment will be further described with reference to these drawings. The biosensor 1 includes a working electrode terminal 3 a for connecting to the working electrode 3, a working electrode terminal 503 a for connecting to the working electrode 503, a counter electrode terminal 504 a for connecting to the counter electrode 504, And a counter electrode terminal 4 a for connection to the counter electrode 4.

  Since the voltage applied to the biosensor is different as shown in FIG. 7, if the blood sample has an arbitrary viscosity, a difference occurs in the working electrode current If. That is, when the viscosity of the sample is high, the measured value obtained from the charge amount Q approaches the true measured value as the biosensor applied voltage increases.

ΔIf = If2-If1 (11)
Since the current difference ΔIf uniquely corresponds to the viscosity as shown in FIG. 7, the current correction amount ΔIf ′ based on the blood viscosity with respect to the expected blood glucose level BSL can also be uniquely determined.
Therefore, different biosensor applied voltages can be applied to the two biosensors, the influence of blood viscosity can be corrected from the measured two blood glucose level data, and an expected accurate blood glucose level can be derived.

  As described above, according to the biosensor device of the present embodiment, a plurality of biosensors having a working electrode and a counter electrode, and desired different voltages are applied between the working electrode and the counter electrode of the plurality of biosensors. Thus, high accuracy can be realized by measuring a current flowing out from the working electrode and providing a biosensor device including a signal processing circuit that specifies the concentration of the measurement target substance from the current value. In this way, even if the biosensor applied voltage is not changed in one biosensor unit, measurement is performed more accurately and more accurately than before by measuring different biosensor applied voltages in a plurality of biosensor units. It becomes possible to measure substances.

  Note that the circuits configuring the first voltage source 505a, the second voltage source 506, the third voltage source 527a, and the fourth voltage source 528 are not limited to the example illustrated in FIG.

  Moreover, as shown in FIG. 9, the biosensor 1 of the biosensor device of this embodiment may be a removable disposable type. Thereby, contamination by the sample measured previously can be prevented.

  In addition, as shown in FIG. 10, the measurement circuit 509 may be removable from the main body as one chip together with the biosensor 1. Normally, the measurement circuit 509 is a circuit dedicated to the substance to be measured. Therefore, by incorporating the measurement circuit 509 into a disposable chip, the main body (from the biosensor device to the biosensor device) is composed of a plurality of biosensor chips for measuring different substances. The portion excluding the sensor chip and the biosensor) can be shared.

(Sixth embodiment)
FIG. 12 is a block circuit diagram showing a biosensor device according to the sixth embodiment of the present invention, and FIG. 13 shows an example of the measurement operation of the biosensor device of this embodiment shown in FIG. 12 over time. FIG.

  As shown in FIG. 12, the biosensor device of this embodiment has a configuration in which the functions of the working electrode and the counter electrode are reversed as compared with the biosensor device of the fifth embodiment shown in FIG.

  That is, the second voltage source 506a and the fourth voltage source 528a have ammeters. The reference voltage source 508 supplies the working electrode control voltage Vpr1 to the first voltage source 505 and the third voltage source 527, and the second voltage source 506a and the fourth voltage source 528a are each provided with a counter electrode control voltage. Vmr1 and the third counter electrode control voltage Vmr2 are supplied.

  The voltage Vp1 of the working electrode 503 and the voltage Vp2 of the working electrode 3 are respectively equal to the working electrode control voltage Vpr1 by the first voltage source 505 and the third voltage source 527.

Vp1 = Vp2 = Vpr1 (12)
Further, the voltage Vm1 of the counter electrode 504 becomes equal to the counter electrode control voltage Vmr1 by the second voltage source 506a. The voltage Vm2 of the counter electrode 4 is equal to the third counter electrode control voltage Vmr2 by the fourth voltage source 528a.

Vm1 = Vmr1 (13)
Vm2 = Vmr2 (14)
Therefore, the biosensor applied voltage Vf1 and the biosensor applied voltage Vf2 are as follows.

Vf1 = Vp1-Vm1 = Vpr1-Vmr1 (15)
Vf2 = Vp2-Vm2 = Vpr1-Vmr2 (16)
That is, the biosensor applied voltages Vf1 and Vf2 are the same as those in the fifth embodiment described above.

  In this state, when a blood sample is applied to biosensor_1, the reaction starts by contact with the reagent. Thus, the counter electrode current Im1 and the counter electrode current Im2 start to be generated, respectively. The second voltage source 506 a having an ammeter measures the counter electrode current Im 1, and outputs a counter electrode current amount signal s 24 as a measurement result to the signal processing circuit 507. At the same time, the fourth voltage source 528 a having an ammeter measures the counter electrode current Im 2 and outputs a counter electrode current amount signal s 25 as a measurement result to the signal processing circuit 507. The signal processing circuit 507 measures the blood glucose level by calculating the counter electrode current amount signal s24 and the counter electrode current amount signal s25.

  In the measurement in the biosensor device of the present embodiment, as shown in FIG. 13, for example, the working electrode control voltage Vpr1, the counter electrode control voltage Vmr1, and the third counter electrode control voltage Vmr2 are constant throughout the measurement period.

  In addition, the graph regarding the charge shown in FIG. 13 shows the time change of the integrated values of the counter electrode current Im1 and the counter electrode current Im2 related to the blood glucose level.

Charge amount Q = ∫ (Im1) dt (17)
Charge amount Q = ∫ (Im2) dt (18)
As described above, when the sample has viscosity, the charge amount Q is uniquely determined with respect to the biosensor applied voltage, so the measurement result of the first biosensor unit 501 and the second biosensor unit From the measurement result at 521, the measurement value can be obtained in the same manner as in the fifth embodiment.

  On the other hand, FIG. 14 is a block circuit diagram showing a circuit configuration example of the first to fourth voltage sources in the biosensor device of the present embodiment shown in FIG. In the example shown in the figure, the output portion of the first voltage source 505 is connected to the working electrode 503 and its own (−) side input portion, and the reference voltage source 508 is connected to the (+) side input portion. This is an operational amplifier 555. The third voltage source 527 is an operational amplifier 557 having an output unit connected to the working electrode 3 and its own (−) side input unit, and a reference voltage source 508 connected to the (+) side input unit. The second voltage source 506a includes an operational amplifier 556 in which the reference voltage source 508 is connected to the (+) side input section and the counter electrode 504 is connected to the (−) side input section, and the output section of the operational amplifier 556 ( -) It is comprised with the feedback resistance 518 provided between the side input parts. The fourth voltage source 528a includes an operational amplifier 558 in which the reference voltage source 508 is connected to the (+) side input unit and the counter electrode 4 is connected to the (−) side input unit, and an output unit of the operational amplifier 558 (−). It is comprised with the feedback resistance 529 provided between the side input parts.

  As described above, even with a configuration in which a substance to be measured is measured via a voltage source connected to the counter electrode, high-precision measurement is possible as in the biosensor devices of the first to fifth embodiments. Become.

(Seventh embodiment)
FIG. 15 is a block circuit diagram showing a biosensor device according to the seventh embodiment of the present invention, and FIG. 16 shows an example of the measurement operation of the biosensor device of this embodiment shown in FIG. 15 over time. FIG.

  As shown in FIG. 15, the biosensor device of the present embodiment is characterized in that an ammeter is added to each of the voltage source connected to each of the two working electrode and the voltage source connected to each of the two counter electrodes. There is in being. Since other configurations are the same as those of the biosensor device of the fifth embodiment or the sixth embodiment, description thereof will be omitted.

  In the biosensor device of this embodiment, when a blood sample is applied to the biosensor 1, the reaction with the reagent starts. As a result, working electrode currents If1 and If2 and counter electrode currents Im1 and Im2 start to be generated. The first voltage source 505a and the third voltage source 527a both having an ammeter measure the working electrode currents If1 and If2, respectively, and the working electrode current amount signals s517 and s17, which are the measurement results, are respectively sent to the signal processing circuit 507. Output. At the same time, the second voltage source 506a and the fourth voltage source 528a both having an ammeter measure the counter electrode currents Im1 and Im2, and the counter electrode current amount signals s24 and s25, which are the measurement results, are respectively signal processing circuits 507. Output to. Thereafter, the signal processing circuit 507 calculates the amount of the measurement substance such as a blood glucose level by calculating the working electrode currents If1 and If2 and the counter electrode currents Im1 and Im2.

  Next, the measurement operation will be described with reference to FIG.

  In the example shown in FIG. 16, as shown in the upper part of FIG. 16, the working electrode control voltage Vpr1, the counter electrode control voltage Vmr1, and the third counter electrode control voltage Vmr2 are constant throughout the measurement period, and Vpr1> Vmr1> Vmr2. Yes.

  In addition, the charge graphs shown in the middle and lower stages of FIG. 16 show time changes in which the working electrode currents If1 and If2 and the counter electrode currents Im1 and Im2 related to the blood glucose level are integrated and added for each biosensor unit.

Charge Q =＝ (If1) dt + ∫ (Im1) dt (19)
Charge Q = ∫ (If2) dt + ∫ (Im2) dt (20)
Then, from the charge amount Q measured for the first biosensor unit 501 and the charge amount Q measured for the second biosensor unit 521, the substance to be measured is measured in the same manner as in the fifth and sixth embodiments. Measurements can be obtained.

  FIG. 17 is a block circuit diagram showing a circuit configuration example of the first to fourth voltage sources in the biosensor device of the present embodiment shown in FIG. Each of the first to fourth voltage sources has the same configuration as that of the first voltage source 505a of the sixth embodiment. However, this is an example of a circuit constituting the voltage source, and the voltage source can be constituted by other circuits.

  In the biosensor device of this embodiment, different biosensor applied voltages are applied to the two biosensor units, and the blood viscosity is determined based on the blood glucose level data of two measured working electrode sides and two counter electrode sides in total. The correct blood glucose level can be derived by correcting the influence. In particular, since the number of blood glucose level data in the biosensor device of this embodiment is twice that of the biosensor devices of the fifth and sixth embodiments, the accuracy is also improved twice.

  As described above, according to the biosensor device of the present embodiment, a plurality of biosensors each having a working electrode and a counter electrode, and a desired voltage is applied between the working electrode and the counter electrode of the plurality of biosensors. By measuring the current flowing out from the working electrode and the current flowing from the counter electrode, the biosensor device is equipped with a signal processing circuit that identifies the concentration of the substance to be measured from the current value, thereby achieving high accuracy. it can.

(Eighth embodiment)
FIG. 18 is a block circuit diagram showing a biosensor device according to the eighth embodiment of the present invention.

  As shown in the figure, the biosensor device of the present embodiment includes a reaction chamber of the first biosensor unit 501 and a second biosensor unit 521 in the biosensor device according to the fifth embodiment shown in FIG. The reaction chamber is connected with a capillary tube. It is assumed that the first biosensor unit 501 and the second biosensor unit have the same performance and the same size and shape of electrodes.

Further, in the measurement circuit 509, the comparison reference voltage Vif is supplied from the reference voltage source 508 to the signal processing circuit 507. FIG. 19 schematically shows the biosensor 31 in the biosensor device of this embodiment shown in FIG. It is a top view. As shown in the figure, the first biosensor unit 501 and the second biosensor unit 521 are vertically (in series) via a capillary tube with respect to a sample spotting portion (a portion into which a sample is placed) of the biosensor device. It is connected to the. Here, the blood sample (body fluid 33) spotted on the sample spotting part first reaches the reaction chamber of the second biosensor part 521 through the capillary 34a, and then passes through the capillary 34b to the first biosensor. It reaches the reaction chamber of the sensor unit 501. Next, the measurement principle of the biosensor device of this embodiment will be described.

  FIG. 20 is a diagram showing an example of the measurement operation of the biosensor device of this embodiment shown in FIG. 18 over time. Here, as shown in the figure, the working electrode control voltage Vpr1 and the counter electrode control voltage Vmr1 having a certain magnitude are supplied to the working electrode terminal and the counter electrode terminal of each biosensor unit throughout the measurement period.

  As shown in the middle and lower stages of FIG. 20, in the biosensor device of this embodiment, blood reaches the reaction chamber of the first biosensor unit 501 after the blood sample reaches the reaction chamber of the second biosensor unit 521. It takes time Δt to reach the sample. This is due to the phenomenon that the speed at which the sample travels through the capillary varies depending on the viscosity of the sample. That is, the higher the viscosity of the sample, the slower the speed of traveling through the capillary, so if the relationship between the viscosity and the moving speed in the capillary is known in advance, the arrival time difference Δt of the blood sample to the two biosensor parts The blood viscosity can be calculated by measuring Furthermore, as in the fifth embodiment, an accurate blood glucose level can be obtained by adding the blood glucose level correction amount ΔIf ′ to the actual measurement value based on the obtained blood viscosity value.

  The capillaries 34b connected to the first biosensor unit 501 and the capillaries 34a connected to the second biosensor unit 521 may have the same size or cross-sectional area, but may be different from each other. Absent. However, it is preferable that the size of the capillary tube 34a and the size of the tube 34b be constant in any part because the viscosity can be easily calculated.

  FIG. 21 is a block circuit diagram showing an example of the circuit configuration of the first to fourth voltage sources in the biosensor device of the present embodiment shown in FIG.

  As described above, according to the biosensor device of the present embodiment, in the biosensor devices described in the fifth to seventh embodiments, a plurality of biosensor portions are sampled spotting portions with the same tubular capillary structure. Since the viscosity of the sample can be corrected by connecting in series, the measurement value can be highly accurate. Further, by combining with a method of correcting the viscosity of the sample from the measured values at a plurality of biosensor units, it is possible to perform a more reliable measurement.

(Ninth embodiment)
FIG. 22 is a plan view showing a biosensor according to the ninth embodiment of the present invention. As shown in the figure, the biosensor 34 of the present embodiment has a configuration in which two biosensor parts having the same characteristics are connected in parallel using capillaries having different thicknesses.

  When configuring a biosensor device including the biosensor 34 of the present embodiment, the same measurement circuit 509 as that of the biosensor device of the eighth embodiment described above is used. Only the features of the biosensor of this embodiment will be described below.

  In the biosensor 34 of the present embodiment, the capillary 35 for supplying a sample to the first biosensor unit having the working electrode 510 and the counter electrode 511 is a second biosensor unit having the working electrode 522 and the counter electrode 523. The width and the cross-sectional area are larger than those of the capillary tube 36 for supplying the sample.

  In general, a phenomenon is known in which the speed of a liquid that travels through a capillary varies depending on the thickness of the capillary, but the biosensor 34 of the present embodiment uses this phenomenon to measure a substance to be measured. That is, according to the biosensor device including the biosensor of this embodiment, the blood viscosity can be calculated by measuring the difference Δt in the arrival time of the blood sample to the two biosensor parts. Further, as in the eighth embodiment, an accurate blood glucose level can be obtained by adding the blood glucose level correction amount ΔIf ′ obtained based on the obtained blood viscosity value to the actual measurement value. .

  As described above, if the biosensor of the present embodiment is used in a biosensor device, measurement with higher accuracy than before can be realized.

(Tenth embodiment)
FIG. 23 is a plan view showing a biosensor according to the tenth embodiment of the present invention. As shown in the figure, the biosensor 37 of the present embodiment includes four biosensor units (first biosensor unit, second biosensor unit, third biosensor unit, And the fourth biosensor unit) have a configuration in which capillaries having different thicknesses are connected in parallel and connected in series to the sample spotting unit.

  When configuring a biosensor device including the biosensor 37 of the present embodiment, the measurement circuit 509 uses four identical biosensor devices of the eighth embodiment described above, thereby providing four biosensors. Corresponding to the part. Only the features of the biosensor of this embodiment will be described below.

  In the biosensor 37 of the present embodiment, the first biosensor unit having the working electrode 510a and the counter electrode 511a and the second biosensor unit having the working electrode 522a and the counter electrode 523a are the biosensor of the eighth embodiment. Similarly to the part, they are connected in series to the sample spotting part.

  The third biosensor unit having the working electrode 510b and the counter electrode 511b and the fourth biosensor unit having the working electrode 522b and the counter electrode 523b are connected to each other in series with respect to the sample spotting unit.

  A capillary 35a for supplying a blood sample to the second biosensor unit and a capillary 35b for connecting the first biosensor unit and the second biosensor unit are connected to the fourth biosensor unit. The width and the cross-sectional area are larger than the capillary 36a for supplying the liquid and the capillary 36b for connecting the third biosensor part and the fourth biosensor part.

  With the above-described configuration, the arrival time differences Δt1, Δt2, and Δt3 of the blood to the four biosensor units are different depending on the phenomenon that the speed of the blood that travels through the capillary varies depending on the thickness of the capillary and the phenomenon that the speed that travels the capillary varies depending on the blood viscosity. Is measured. The blood viscosity can be calculated by measuring the difference between these arrival times. As in the eighth embodiment, an accurate blood sugar level can be obtained by adding the blood sugar level correction amount ΔIf ′ obtained based on the obtained blood viscosity value to the actual measurement value.

  In particular, if the biosensor of this embodiment is used, the data amount of the arrival time difference Δt is obtained three times as compared with the eighth and ninth embodiments, so that the blood glucose level correction amount ΔIf ′ accuracy is improved three times. As a result, more accurate measurement can be realized.

  As described above, if the biosensor of this embodiment is used in the biosensor devices of the fifth to seventh embodiments, it is possible to achieve high accuracy of measurement values.

(Eleventh embodiment)
FIG. 24 is a plan view showing a biosensor according to an eleventh embodiment of the present invention.

  The biosensor 38 of the present embodiment is composed of two biosensor units having different performances. For example, in the example illustrated in FIG. 24, the working electrode 522 of the second biosensor unit has a larger planar area than the working electrode 510 of the first biosensor unit, and the counter electrode 523 of the second biosensor unit has the first electrode. The planar area is larger than the counter electrode 511 of the biosensor unit. As a result, the contact area between each electrode of the second biosensor unit and the blood sample is increased, so that the reaction time of glucose catalyzed by the enzyme is shortened as compared with the first biosensor unit. In addition, when comprising the biosensor apparatus provided with the biosensor of this embodiment, as the measurement circuit 509, the same thing as any one of the biosensor apparatus of the 5th-10th embodiment mentioned above is used.

  The biosensor device of the present embodiment has a configuration composed of two biosensor units having different performances, so that the time difference Δt until the measurement value is obtained in each biosensor unit and the working electrode currents If1 and If2 Blood viscosity can be calculated. A more accurate blood sugar level can be obtained by adding the blood sugar level correction amount ΔIf ′ obtained from the obtained blood viscosity value to the actual measurement value.

  As described above, high accuracy can be realized by applying the biosensor of this embodiment to the fifth to tenth biosensor devices.

  24 shows an example in which two types of biosensor units are included in the biosensor 38, the biosensor may include three or more types of biosensor units having different characteristics. In this case, since the number of Δt that can be measured increases, it is possible to measure with higher accuracy.

  As described above, the biosensor device of the present invention is used for measuring substances that generate electrons by chemical reaction or enzymatic reaction, such as blood glucose and lactic acid, and is very useful for medical development.

FIG. 1 is a block circuit diagram showing a biosensor device according to the first embodiment of the present invention. FIG. 2 is a diagram illustrating a relationship between the biosensor applied voltage Vf1 and the charge amount Q in the biosensor device according to the first embodiment. FIG. 3 is a diagram showing the relationship between the biosensor applied voltage Vf1 and the charge amount Q in the biosensor device according to the second embodiment of the present invention. FIG. 4 is a diagram showing the relationship between the biosensor applied voltage Vf1 and the charge amount Q in the biosensor device according to the third embodiment of the present invention. FIG. 5 is a block circuit diagram showing a biosensor device according to the fourth embodiment of the present invention. FIG. 6 is a circuit diagram showing a biosensor device according to the fifth embodiment of the present invention. FIG. 7 is a diagram illustrating an example of the measurement operation of the biosensor device according to the fifth embodiment over time. FIG. 8 is a block circuit diagram showing a circuit configuration example of the first to fourth voltage sources in the biosensor device according to the fifth embodiment. FIG. 9 is a plan view schematically showing a configuration example of the biosensor in the biosensor device according to the fifth embodiment. FIG. 10 is a diagram illustrating a configuration example of a biosensor chip in which the biosensor and the measurement circuit according to the fifth embodiment are integrated into one chip. FIG. 11 is a diagram in which the principle of the present invention is entered in the performance diagram of the conventional biosensor shown in FIG. FIG. 12 is a block circuit diagram showing a biosensor device according to the sixth embodiment of the present invention. FIG. 13 is a diagram illustrating an example of the measurement operation of the biosensor device according to the sixth embodiment over time. FIG. 14 is a block circuit diagram showing a circuit configuration example of the first to fourth voltage sources in the biosensor device according to the sixth embodiment. FIG. 15 is a block circuit diagram showing a biosensor device according to the seventh embodiment of the present invention. FIG. 16 is a diagram illustrating an example of the measurement operation of the biosensor device according to the seventh embodiment over time. FIG. 17 is a block circuit diagram showing a circuit configuration example of the first to fourth voltage sources in the biosensor device according to the seventh embodiment. FIG. 18 is a block circuit diagram showing a biosensor device according to the eighth embodiment of the present invention. FIG. 19 is a plan view schematically showing a biosensor in the biosensor device of the eighth embodiment. FIG. 20 is a diagram illustrating an example of the measurement operation of the biosensor device according to the eighth embodiment over time. FIG. 21 is a block circuit diagram showing an example of the circuit configuration of the first to fourth voltage sources in the biosensor device according to the eighth embodiment. FIG. 22 is a plan view showing a biosensor according to the ninth embodiment of the present invention. FIG. 23 is a plan view showing a biosensor according to the tenth embodiment of the present invention. FIG. 24 is a plan view showing a biosensor according to an eleventh embodiment of the present invention. FIG. 25 is a block circuit diagram showing the structure of a conventional biosensor device. FIG. 26 is a diagram showing the measurement operation of the conventional biosensor device over time. FIG. 27 is a block circuit diagram showing an example of the circuit configuration of the first voltage source and the second voltage source in the conventional biosensor device. FIG. 28 is a plan view showing a configuration example of a biosensor in a conventional biosensor device. FIG. 29 is a plan view showing a configuration example of a biosensor chip in a conventional biosensor device. FIG. 30 is a diagram schematically illustrating a relationship between a blood glucose level, a blood sample viscosity, and a biosensor applied voltage Vf1 in a conventional biosensor device. FIG. 31 is a diagram showing an example of the measurement operation of the conventional biosensor device over time.

Explanation of symbols

1, 31, 34, 37, 38 Biosensor 3,503 Working electrode 3a, 503a Working electrode 4,504 Counter electrode 4a, 504a Counter electrode 5,518,529 Feedback resistor 6 Voltage source with low-pass filter 8 ΔΣ modulator 9 Capacitance 20 Biosensor chip 33 Body fluid 34a, 34b, 35, 35a, 35b, 36, 36a, 36b Capillary 501 First biosensor section 505, 505a First voltage source 506, 506a Second voltage source 507 Signal processing Circuit 508 Reference voltage source 509 Measuring circuit 510, 510a, 510b Working electrode 511, 511a, 511b Counter electrode 521 Second biosensor section 522, 522a, 522b Working electrode 523, 523a, 523b Counter electrode 527, 527a Third voltage source 528 , 528a Fourth voltage source 550, 5 1,552,553,555,557,558 Operational amplifier If1, If2 Working electrode current Im1, Im2 Counter electrode current Vf1, Vf2 Biosensor applied voltage Vmr1 Counter electrode control voltage Vmr2 Third counter electrode control voltage Vmr3 Second counter electrode control voltage Vpr1 Action Pole control voltage s24, s25 Counter electrode current signal s517, s17 Working electrode current signal

Claims (2)

A plurality of biosensor units each including a working electrode and a counter electrode facing the working electrode with an interval for allowing the fluid to be tested including the substance to be measured to flow; and for spotting the fluid to be tested A biosensor having a sample spotting portion and a capillary for supplying the fluid to be tested to each biosensor portion;
A voltage is applied between each working electrode and the counter electrode of the biosensor unit during measurement, and the concentration of the substance to be measured is determined based on the current flowing from the working electrode or the counter electrode of each biosensor unit. A biosensor device comprising a measurement circuit for measuring,
The plurality of biosensor units are connected to each other in parallel when viewed from the sample spotting unit by the capillaries, and the capillaries for supplying the fluid to be tested to the biosensor units have different sizes. Biosensor device. A plurality of biosensor units including a working electrode, a counter electrode facing the working electrode with a space for allowing the fluid to be tested containing the substance to be measured to flow, and a sample for spotting the fluid to be tested A biosensor having a spotting section and a capillary for supplying the fluid to be tested to each of the plurality of biosensor sections,
Each of the plurality of biosensor units is connected in parallel with each other when viewed from the sample spotting unit by the capillary, and the capillaries for supplying the fluid to be tested to the biosensor units have different sizes. A biosensor.

Images